title: Protein loop compaction and the origin of the effect of arginine and glutamic acid mixtures on solubility, stability and transient oligomerization of proteins.
abstract: Addition of a 50 mM mixture of L: -arginine and L: -glutamic acid (RE) is extensively used to improve protein solubility and stability, although the origin of the effect is not well understood. We present Small Angle X-ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) results showing that RE induces protein compaction by collapsing flexible loops on the protein core. This is suggested to be a general mechanism preventing aggregation and improving resistance to proteases and to originate from the polyelectrolyte nature of RE. Molecular polyelectrolyte mixtures are expected to display long range correlation effects according to dressed interaction site theory. We hypothesize that perturbation of the RE solution by dissolved proteins is proportional to the volume occupied by the protein. As a consequence, loop collapse, minimizing the effective protein volume, is favored in the presence of RE.
authors.affiliation: Laboratory of Biomolecular NMR, Institute for Research in Biomedicine, Parc Científic de Barcelona, Spain.
authors.forename: Jascha
authors.initials: J
authors.lastname: Blobel
authors.forename: Ulrika
authors.initials: U
authors.lastname: Brath
authors.forename: Pau
authors.initials: P
authors.lastname: Bernadó
authors.forename: Carl
authors.initials: C
authors.lastname: Diehl
authors.forename: Lidia
authors.initials: L
authors.lastname: Ballester
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sornosa
authors.forename: Mikael
authors.initials: M
authors.lastname: Akke
authors.forename: Miquel
authors.initials: M
authors.lastname: Pons
mesh_terms: D001120:Arginine / Q000737:chemistry*; D001704:Biopolymers / Q000737:chemistry*; D002919:Chymotrypsinogen / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry*; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D058619:Maltose-Binding Proteins / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D015999:Multivariate Analysis; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*; D053838:Scattering, Small Angle; D012995:Solubility; D022021:Tacrolimus Binding Proteins / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D001704:Biopolymers; D058619:Maltose-Binding Proteins; D011506:Proteins; D018698:Glutamic Acid; D002919:Chymotrypsinogen; D001120:Arginine; D022021:Tacrolimus Binding Proteins